Oxidative assets toward biomolecules and cytotoxicity of new oxindolimine-copper(II) and zinc(II) complexes
| Autor: | Aline Monteiro Lino Zaballa, Maria Rosa Ciriolo, Ana Maria da Costa Ferreira, Carla C. Oliveira, Marcela Bach Prieto, Queite A. de Paula, Maurício Cavicchioli, Patrizia Civitareale |
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| Rok vydání: | 2019 |
| Předmět: |
antiproliferative activity
Circular dichroism Stereochemistry ZINCO 010402 general chemistry 01 natural sciences Inorganic Chemistry 03 medical and health sciences chemistry.chemical_compound lcsh:Inorganic chemistry 030304 developmental biology chemistry.chemical_classification Gel electrophoresis 0303 health sciences Reactive oxygen species DNA cleavage biology Spin trapping Chemistry Topoisomerase oxindolimine–metal complexes Ligand (biochemistry) lcsh:QD146-197 0104 chemical sciences biology.protein HSA oxidation cytotoxicity isatin-derived ligands Ethidium bromide DNA |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Inorganics, Vol 7, Iss 2, p 12 (2019) Inorganics Volume 7 Issue 2 |
| Popis: | A new oxindolimine ligand derived from isatin (1H-indole-2,3-dione) and 2-aminomethylbenzimidazole was synthesized, leading to two novel complexes after metalation with copper(II) perchlorate or zinc(II) chloride, [Cu(isambz)2](ClO4)2 (complex 1) and [Zn(isambz)Cl2] (complex 2). This new ligand was designed as a more lipophilic compound, in a series of oxindolimine&ndash metal complexes with antitumor properties, having DNA, mitochondria, and some proteins, such as CDK1 kinase and topoisomerase IB, as key targets. The new complexes had their reactivity to human serum albumin (HSA) and DNA, and their cytotoxicity toward tumor cells investigated. The binding to CT-DNA was monitored by circular dichroism (CD) spectroscopy and fluorescence measurements using ethidium bromide in a competitive assay. Consequent DNA cleavage was verified by gel electrophoresis with complex 1, in nmolar concentrations, with formation of linear DNA (form III) after 60 min incubation at 37 ° C, in the presence of hydrogen peroxide, which acts as a reducing agent. Formation of reactive oxygen species (ROS) was observed, monitored by spin trapping EPR. Interaction with HSA lead to &alpha helix structure disturbance, and formation of a stable radical species (HSA&ndash Tyr· ) and carbonyl groups in the protein. Despite showing oxidative ability to damage vital biomolecules such as HSA and DNA, these new complexes showed moderate cytotoxicity against hepatocellular carcinoma (HepG2) and neuroblastoma (SHSY5Y) cells, similarly to previous compounds in this series. These results confirm DNA as an important target for these compounds, and additionally indicate that oxidative damage is not the leading mechanism responsible for their cytotoxicity. Additionally, this work emphasizes the importance of ligand characteristics and of speciation in activity of metal complexes. |
| Databáze: | OpenAIRE |
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